Research publications - Association for Research in Nervous and Mental Disease最新文献

{"title":"Cellular physiology of hypoxia of the mammalian central nervous system.","authors":"G G Somjen,&nbsp;P G Aitken,&nbsp;G Czéh,&nbsp;J Jing,&nbsp;J N Young","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>We began this brief review with a condensed summary of the responses of mammalian central neurons to hypoxic insult and then described our recent studies aimed at solving the biophysical basis of these responses. We distinguished three main phases of cerebral hypoxia. First, withdrawal of oxygen is rapidly followed by failure of synaptic transmission. Second, there is massive depolarization of cells, resembling the SD of Leão. Timely reoxygenation can still restore function. If, however, SD-like depolarization continues beyond a critical time, the third phase, irreversible loss of responsiveness, sets in. Cell loss is initially highly selective. Finally, upon reoxygenation, some neurons, which at first appear normal, then undergo a sequence of changes leading to delayed neuron degeneration. The principal cause of early synaptic failure is the depression of synaptic potentials. This can be attributed to reduced release of transmitter substance, in turn caused by failure of the opening of voltage-dependent calcium channels in presynaptic terminals. Calcium-channel failure is probably caused either by a rise of intracellular free calcium activity, depletion of adenosine triphosphate (ATP) levels in presynaptic terminals, or a combination of both. Conduction block in presynaptic fiber terminals can, in some situations, contribute to synaptic failure. In some (postsynaptic) neuron membranes, conductance for potassium increases, raising the firing threshold and hastening the failure of excitatory synaptic transmission. Hypoxic SD-like depolarization is a complex but stereotyped and explosive event. The longer the depolarization lasts, the smaller the chance for functional recovery after reoxygenation. The least likely to recover are those cells that undergo SD the earliest. Prolonged intracellular accumulation of free calcium, admitted into the cells by the SD-like membrane change, plays a key role in causing neuron damage (Fig. 8). Some antagonists of NMDA receptors and blockers of sodium, calcium, and potassium channels influence the onset and magnitude of SD-like hypoxic depolarization, but no known drug prevents it. The irreversible neuron damage that occurs during hypoxia should be distinguished from delayed postischemic injury that occurs after initial apparent recovery. The delayed process can proceed even in the controlled environment of isolated hippocampal tissue slices, but it can be prevented in vitro by NMDA receptor antagonist drugs. In the clinical management of cerebral ischemia not only the intrinsic neuronal degenerative process, but also the deteriorating extracellular milieu, needs to be treated, and the latter may not be improved by NMDA receptor blockade.(ABSTRACT TRUNCATED AT 400 WORDS)</p>","PeriodicalId":76423,"journal":{"name":"Research publications - Association for Research in Nervous and Mental Disease","volume":"71 ","pages":"51-65"},"PeriodicalIF":0.0,"publicationDate":"1993-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19366074","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mitochondrial dysfunction as a mechanism of CNS injury.","authors":"S DiMauro,&nbsp;S Simonetti,&nbsp;X Chen,&nbsp;V Petruzzella,&nbsp;M Hirano,&nbsp;S Shanske,&nbsp;C T Moraes,&nbsp;E A Schon","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":76423,"journal":{"name":"Research publications - Association for Research in Nervous and Mental Disease","volume":"71 ","pages":"67-79"},"PeriodicalIF":0.0,"publicationDate":"1993-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19401543","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anoxic injury of central myelinated axons: ionic mechanisms and pharmacology.","authors":"B R Ransom,&nbsp;S G Waxman,&nbsp;P K Stys","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":76423,"journal":{"name":"Research publications - Association for Research in Nervous and Mental Disease","volume":"71 ","pages":"121-51"},"PeriodicalIF":0.0,"publicationDate":"1993-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19402372","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Factors affecting proviral expression in primary cells grafted into the CNS.","authors":"M Schinstine,&nbsp;F H Gage","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":76423,"journal":{"name":"Research publications - Association for Research in Nervous and Mental Disease","volume":"71 ","pages":"311-23"},"PeriodicalIF":0.0,"publicationDate":"1993-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19402378","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacological modification of axon membrane molecules and cell transplantation as approaches to the restoration of conduction in demyelinated axons.","authors":"J D Kocsis,&nbsp;J A Black,&nbsp;S G Waxman","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":76423,"journal":{"name":"Research publications - Association for Research in Nervous and Mental Disease","volume":"71 ","pages":"265-92"},"PeriodicalIF":0.0,"publicationDate":"1993-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19366072","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Free radicals in CNS injury.","authors":"E D Hall,&nbsp;J M Braughler","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>This chapter has reviewed the current state of knowledge regarding the occurrence and possible role of oxygen radical generation and lipid peroxidation in experimental models of acute CNS injury. Although much work remains, four criteria that are logically required to establish the pathophysiological importance of oxygen radical reactions have been met, at least in part. First of all, oxygen radical generation and lipid peroxidation appear to be early biochemical events subsequent to CNS trauma. Second, a growing body of direct or circumstantial evidence suggests that oxygen radical formation and lipid peroxidation are linked to pathophysiological processes such as hypoperfusion, edema, axonal conduction failure, failure of energy metabolism, and anterograde (wallerian) degeneration. Third, there is a striking similarity between the pathology of blunt mechanical injury to CNS tissue and that produced by chemical induction of peroxidative injury. Fourth, and most convincing, is the repeated observation that compounds that inhibit lipid peroxidation or scavenge oxygen radicals can block posttraumatic pathophysiology and promote functional recovery and survival in experimental studies. Nevertheless, the significance of oxygen radicals and lipid peroxidation ultimately depends on whether it can be demonstrated that early application of effective antifree radical or antiperoxidative agents can promote survival and neurological recovery after CNS injury and stroke in humans. The results of the NASCIS II clinical trial, which have shown that an antioxidant dosing regimen with methylprednisolone begun within 8 hr after spinal cord injury can significantly enhance chronic neurological recovery, strongly supports the significance of lipid peroxidation as a posttraumatic degenerative mechanism. However, ongoing Phase III trials with the more selective and effective antioxidant U74006F (tirilazad mesylate) will give a more clear-cut answer as to the therapeutic importance of inhibition of posttraumatic free radical reactions in the injured CNS.</p>","PeriodicalId":76423,"journal":{"name":"Research publications - Association for Research in Nervous and Mental Disease","volume":"71 ","pages":"81-105"},"PeriodicalIF":0.0,"publicationDate":"1993-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19366075","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Calcium and glutamate-induced cortical neuronal death.","authors":"D W Choi,&nbsp;D M Hartley","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":76423,"journal":{"name":"Research publications - Association for Research in Nervous and Mental Disease","volume":"71 ","pages":"23-34"},"PeriodicalIF":0.0,"publicationDate":"1993-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19086665","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular and Cellular Approaches to the Treatment of Neurological Disease. Symposium proceedings. New York City, New York, December 6-7, 1991.","authors":"","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":76423,"journal":{"name":"Research publications - Association for Research in Nervous and Mental Disease","volume":"71 ","pages":"1-374"},"PeriodicalIF":0.0,"publicationDate":"1993-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19086094","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neurobiological mechanisms in cocaine and opiate dependence.","authors":"G F Koob","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":76423,"journal":{"name":"Research publications - Association for Research in Nervous and Mental Disease","volume":"70 ","pages":"79-92"},"PeriodicalIF":0.0,"publicationDate":"1992-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"12485681","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Current concepts of addiction.","authors":"J H Jaffe","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":76423,"journal":{"name":"Research publications - Association for Research in Nervous and Mental Disease","volume":"70 ","pages":"1-21"},"PeriodicalIF":0.0,"publicationDate":"1992-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"12705102","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}